The present invention relates to a process for preparing optically-active amino acid (di)benzyl esters, to a process for preparing optically-active amino acid (di)benzyl ester sulfonates, and to optically-active amino acid (di)ester tartramic acids and a process for preparing them.
Optically-active amino acid benzyl esters, optically-active amino acid dibenzyl esters and their sulfonates are useful for materials for medicines and agricultural chemicals, and the present invention relates to processes for preparing amino acid benzyl esters and amino acid dibenzyl esters of high optical purity through simple operations not lowering the optical purity of the optically-active amino acids. Notonly optically-active xcex1-amino acid ester tartramic acids and optically-active xcex1-amino acid diester tartramic acids are useful for materials for medicines and agricultural chemicals, but also they are easy to optically resolve as having a plurality of asymmetric carbon atoms, and, in addition, their optical purity can be accurately determined through HPLC analysis with ordinary reversed-phase columns.
A method of producing optically-active amino acid benzyl esters by reacting an optically-active amino acid with excessive benzyl alcohol in benzene in the presence of paratoluenesulfonic acid monohydrate therein in a mode of continuous azeotropic dehydration (Dean-Stark reaction) is known from long ago. (Journal of Organic Chemistry, Vol. 22, page 1515 (1957).) For thermally unstable amino acids, also known is a method of producing optically-active amino acid benzyl esters, which comprises adding benzyl alcohol and dimethylaminopyridine to an optically-active amino acid of which the amino group is protected with a tertiary butoxycarbonyl group (Boc group) or the like, dehydrating it with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide with stirring in a solvent of dichloromethane at 0xc2x0 C. to thereby prepare an N-protected amino acid benzyl ester, and thereafter removing the protective group from it. (Journal of Organic Chemistry, Vol. 47, page 1962 (1982).) On the other hand, optically-active xcex1-amino acid ester tartramic acids, and optically-active xcex1-amino acid diester tartramic acids are novel compounds, and no one knows how to produce them.
However, the method of continuous azeotropic dehydration (Dean-Stark reaction) of reacting an optically-active amino acid with excessive benzyl alcohol in benzene in the presence of paratoluenesulfonic acid monohydrate therein is accompanied by racemization. Especially for amino acids that require high temperature and take long time for esterification, benzyl esters of high optical purity are difficult to obtain from them. The method of first esterifying an optically-active amino acid of which the amino group has been protected, with benzyl alcohol and then removing the protective group from the resulting ester is not accompanied by racemization as the condition for esterification therein is mild, but it requires complicated operations. Therefore, the method is problematic, if used for producing amino acid benzyl esters and amino acid dibenzyl esters of high optical purity on an industrial scale.
The problem with the present invention is how to produce amino acid benzyl esters and amino acid dibenzyl esters of high optical purity through simple operations on an industrial scale, not lowering the optical purity of optically-active amino acids used as starting materials. Optically-active amino acid ester tartramic acids and optically-active amino acid diester tartramic acids are novel substances.
In producing optically-active amino acid benzyl esters or optically-active amino acid dibenzyl esters by reacting an optically-active amino acid with a benzyl alcohol in the presence of an acid catalyst, when a hydrazine is present in the reaction system, or when the reaction is effected in the absence of oxygen, or when a hydrazine is present in the reaction system and the reaction is effected in the absence of oxygen, then optically-active amino acid benzyl esters or dibenzyl esters of high optical purity can be obtained.
In addition, when an optically-active diacyltartaric anhydride is reacted with an optically-active amino acid ester or diester, or is reacted with a racemic amino acid ester or diester and then optically resolved, then optically-active amino acid ester tartramic acids or optically-active amino acid diester tartramic acids can be produced.